Vitamin B12 Supplementation During Pregnancy on Cognitive Development

Cobalamin (Vitamin B12) deficiency is common in many low- and middle-income countries. This is not surprising as the main source of vitamin B12 is animal source foods, which are expensive and for cultural and religious reasons often not eaten at all. We have in several studies in women and children demonstrated that poor vitamin B12 status is common in South Asia. There is also compelling evidence that vitamin B12 deficiency occurs frequently in many other settings including pregnant women .

Case studies have demonstrated harmful effects of severe vitamin B12 deficiency on the developing infant brain.The consequences of mild or subclinical vitamin deficiency are less clear but it has been shown to be associated with decreased cognitive performance in both elderly and children.

Three randomized controlled trials (RCT) have measured the effect of vitamin B12 supplementation on neurodevelopment in children: In a Norwegian trial, an intramuscular injection of B12 substantially improved motor development in six weeks old infants after one month. Another intervention study in low birth weight children in Norway recently confirmed these findings. The infants in these studies had evidence of suboptimal vitamin B12 status, but none were severely deficient. We found a beneficial effect of vitamin B12 supplementation for six months on neurodevelopment in young North Indian children.

During pregnancy, vitamin B12 is concentrated in the fetus and stored in the liver. Infants born to vitamin B12-replete mothers have stores of vitamin B12 that are adequate to sustain them for the first several months postpartum. Consequently, vitamin B12 deficiency rarely occurs before the infant is about four months old if the mother has adequate vitamin B12 status during pregnancy. However, many infants of vitamin B12-deficient breastfeeding mothers are vulnerable to B12 deficiency from an early age.

In this project we will randomise Nepalese women to receive a supplement containing 50µg cobalamin or a placebo from early pregnancy until 6 months postpartum.

Hypothesis to be tested

Principal hypothesis: Daily administration of vitamin B12 to pregnant women from early pregnancy until 6 months postpartum will:

• Increase the scores of the Bayley Scales of Infant and Toddler Development, 3rd ed. (Bayley-III) by 0.25 SD points measured at 6 and 12 months of age.
• Increase length for age and weight for length by 0.2 z-scores at 12 months of age.

Other hypotheses to be tested (dependent on additional funding):

• Daily maternal administration of vitamin B12 from the start of the early pregnancy and for 6 months postpartum improves the hemoglobin concentration in the mother and infant.
• Daily maternal administration of vitamin B12 from early pregnancy and for 6 months postpartum improves plasma vitamin B12 concentration and reduces plasma total homocysteine and methylmalonic acid concentration in the mother and infant.
• Daily maternal administration of vitamin B12 from early pregnancy and for 6 months postpartum improves insulin sensitivity in the offspring.

Inclusion criteria

• Pregnant mother in early pregnancy and not later than 15 weeks of pregnancy.
• Current resident and plan to reside in Bhaktapur district for at least the next 2 years.
• Age of mother between 18 and 40 years.
• Consent to participate in the study.

Exclusion criteria

• Taking or plan to take dietary or multivitamin supplements containing vitamin B12.
• Known case of chronic disease like asthma, tuberculosis, diabetes, hypertension, hypo or hyperthyroidism or others
• Known case of current high risk pregnancy
• Severe anemia (hemoglobin concentration <7 g/dL).
• Where the study doctor finds it necessary to treat the woman with vitamin B12 or vitamin B12 containing supplements